Melanoma-like features in pediatric longitudinal melanonychia: A systematic review and meta-analysis.

BACKGROUND: Pediatric longitudinal melanonychia (LM) can exhibit atypical features that mimic red-flag signs for subungual melanoma in adults and lead to diagnostic uncertainty. Nail biopsy may be unnecessary if clinical inspection and dermoscopy suggest a benign nature. METHODS: We searched PubMed and Embase from inception to February 2023 for studies of any design reporting either the number or proportion of clinical and dermoscopic features in at least five children (≤18 years) with LM. Non-English articles, reviews, and abstracts were excluded. We performed a systematic review and meta-analysis to collate all existing data. RESULTS: A total of 1218 articles were screened and 24 studies with 1391 pediatric patients were included. Nevus was the most common diagnosis (86.3%). The most prevalent sites were fingernails (76.2%) and first digits (45.4%). Pooled proportions of common features were: dark-color bands (69.8%), multi-colored bands (47.6%), broad bandwidth (41.1%), pseudo-Hutchinson sign (41.0%), irregular patterns (38.1%), Hutchinson sign (23.7%), dots and globules (22.5%), nail dystrophy (18.2%), and triangular sign (10.9%). Outcomes included progression (widening or darkening, 29.9%), stability (23.3%), and spontaneous regression (narrowing or fading, 19.9%). Only eight cases of subungual melanoma in situ were reported, and no invasive melanomas were identified. CONCLUSION: Although atypical characteristics are common in pediatric LM, the probability of malignant transformation is exceedingly low. Appropriate evaluation and management of pediatric LM includes careful clinical and dermoscopic inspection with attention to benign features followed by long-term interval follow-up.

JAK Inhibitors for the Treatment of Pediatric Alopecia Areata.

Alopecia areata is a common autoimmune condition that disproportionately affects children and can significantly hinder quality of life. Few safe and effective therapies are available for the treatment of severely affected pediatric patients. JAK inhibitors have been recently established as an effective and well-tolerated therapy in adults, but there are limited data regarding the use of JAK inhibitors to treat alopecia areata in children. Here, we review the available literature regarding the use of JAK inhibitors in children in dermatology and across other medical disciplines.

Epitranscriptomic profiling across cell types reveals associations between APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function.

Epitranscriptomics refers to posttranscriptional alterations on an mRNA sequence that are dynamic and reproducible, and affect gene expression in a similar way to epigenetic modifications. However, the functional relevance of those modifications for the transcript, the cell, and the organism remain poorly understood. Here, we focus on RNA editing and show that Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-1 (APOBEC1), together with its cofactor RBM47, mediates robust editing in different tissues. The majority of editing events alter the sequence of the 3'UTR of targeted transcripts, and we focus on one cell type (monocytes) and on a small set of highly edited transcripts within it to show that editing alters gene expression by modulating translation (but not RNA stability or localization). We further show that specific cellular processes (phagocytosis and transendothelial migration) are enriched for transcripts that are targets of editing and that editing alters their function. Finally, we survey bone marrow progenitors and demonstrate that common monocyte progenitor cells express high levels of APOBEC1 and are susceptible to loss of the editing enzyme. Overall, APOBEC1-mediated transcriptome diversification is required for the fine-tuning of protein expression in monocytes, suggesting an epitranscriptomic mechanism for the proper maintenance of homeostasis in innate immune cells.

Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3' UTRs.

Apolipoprotein B-editing enzyme, catalytic polypeptide-1 (APOBEC1) is a cytidine deaminase initially identified by its activity in converting a specific cytidine (C) to uridine (U) in apolipoprotein B (apoB) mRNA transcripts in the small intestine. Editing results in the translation of a truncated apoB isoform with distinct functions in lipid transport. To address the possibility that APOBEC1 edits additional mRNAs, we developed a transcriptome-wide comparative RNA sequencing (RNA-Seq) screen. We identified and validated 32 previously undescribed mRNA targets of APOBEC1 editing, all of which are located in AU-rich segments of transcript 3' untranslated regions (3' UTRs). Further analysis established several characteristic sequence features of editing targets, which were predictive for the identification of additional APOBEC1 substrates. The transcriptomics approach to RNA editing presented here dramatically expands the list of APOBEC1 mRNA editing targets and reveals a novel cellular mechanism for the modification of transcript 3' UTRs.

Diverse functions for DNA and RNA editing in the immune system.

Polynucleotide DNA and RNA editing enzymes alter nucleic acid sequences and can thereby modify encoded informational content. Two major families of polynucleotide editing enzymes, the AID/APOBEC cytidine deaminases (which catalyze the deamination of cytidine to uridine) and the adenosine deaminases acting on RNA (ADARs, which catalyze the deamination of adenosine to inosine), function in a variety of host defense mechanisms. These enzymes act in innate and adaptive immune pathways, with both host and pathogen targets. DNA editing by the cytidine deaminase AID mediates immunoglobulin somatic hypermutation and class switch recombination, providing the antibody response with the flexibility and diversity to defend against an almost limitless array of varied and rapidly adapting pathogenic challenges. Other cytidine deaminases (APOBEC3) restrict retroviral infection by editing viral retrogenomes. Adenosine deaminases (ADARs) shape innate immune responses by modifying host transcripts that encode immune effectors and their regulators. Here we review current knowledge of polynucleotide DNA and RNA editors with a focus on these and other functions they serve in the immune system.

Effects of a supplemental Spanish oral language program on sentence length, complexity, and grammaticality in Spanish-speaking children attending English-only preschools.

PURPOSE: The purpose of this study was to examine the effects of a supplemental Spanish language instruction program for children who spoke Spanish as their native language and were attending English-only preschool programs. Specifically, the study evaluated the program's effects on the children's Spanish sentence length in words, subordination index, and grammaticality of sentences. METHOD: Forty-five Spanish-speaking children attending English-only prekindergarten classrooms were selected for study. Of those, 15 children received 30 min of Spanish instruction 5 days a week for 16 weeks. The program targeted 5-10 vocabulary words a week, dialogic book reading, phonemic awareness, and letter knowledge. The remaining 30 children participated in regular preschool English instruction. Students were evaluated before intervention, immediately after intervention, and 4 months following intervention. RESULTS: Repeated measures analyses of variance indicated that the children who received the small-group supplemental Spanish language instruction made significant gains in their Spanish sentence length in words and subordination index when compared to those receiving regular English-only classroom instruction. There were no differences in the children's grammaticality of sentences. DISCUSSION AND CLINICAL IMPLICATIONS: The findings demonstrate that a daily short native language program has significant effects on sentence length in words and subordination index in English language learners who are attending English-only preschool programs.

SHP-2 activates signaling of the nuclear factor of activated T cells to promote skeletal muscle growth.

The formation of multinucleated myofibers is essential for the growth of skeletal muscle. The nuclear factor of activated T cells (NFAT) promotes skeletal muscle growth. How NFAT responds to changes in extracellular cues to regulate skeletal muscle growth remains to be fully defined. In this study, we demonstrate that mice containing a skeletal muscle-specific deletion of the tyrosine phosphatase SHP-2 (muscle creatine kinase [MCK]-SHP-2 null) exhibited a reduction in both myofiber size and type I slow myofiber number. We found that interleukin-4, an NFAT-regulated cytokine known to stimulate myofiber growth, was reduced in its expression in skeletal muscles of MCK-SHP-2-null mice. When SHP-2 was deleted during the differentiation of primary myoblasts, NFAT transcriptional activity and myotube multinucleation were impaired. Finally, SHP-2 coupled myotube multinucleation to an integrin-dependent pathway and activated NFAT by stimulating c-Src. Thus, SHP-2 transduces extracellular matrix stimuli to intracellular signaling pathways to promote skeletal muscle growth.